cooperative binding of transcription factors promotes bimodal gene expression response合作结合转录因子基因表达促进双峰响应.pdf

Cooperative Binding of Transcription Factors Promotes Bimodal Gene Expression Response 1 2 1 Pablo S. Gutierrez , Diana Monteoliva , Luis Diambra * ´ 1 Centro Regional de Estudios Genmicos, Universidad Nacional de La Plata, Florencio Varela, Buenos Aires, Argentina, 2 Instituto de Fısica, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina Abstract In the present work we extend and analyze the scope of our recently proposed stochastic model for transcriptional regulation, which considers an arbitrarily complex cis-regulatory system using only elementary reactions. Previously, we determined the role of cooperativity on the intrinsic fluctuations of gene expression for activating transcriptional switches, by means of master equation formalism and computer simulation. This model allowed us to distinguish between two cooperative binding mechanisms and, even though the mean expression levels were not affected differently by the acting mechanism, we showed that the associated fluctuations were different. In the present generalized model we include other regulatory functions in addition to those associated to an activator switch. Namely, we introduce repressive regulatory functions and two theoretical mechanisms that account for the biphasic response that some cis-regulatory systems show to the transcription factor concentration. We have also extended our previous master equation formalism in order to include protein production by stochastic translation of mRNA. Furthermore, we examine the graded/binary scenarios in the context of the interaction energy between transcription factors. In this sense, this is th